04 diagnostic value of cytohistopathologic specimens obtaine

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Diagnostic Value of CytohistopathologicSpecimens obtained by Bronchoscopy

4th Annual CME, MAMC, Delhi13th October, 2012

Harsh Mohan, MD, FAMS, FICPath, FUICC

GMCH-32, [email protected]


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Lay out

Introduction

Bronchoscopy

Pathologic specimens

Cytologic features

Histopathologic features

Cytohistopathologic correlation: our experience Representative cases: neoplasms, nonneoplastic

(infections, others)

Take home message


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Introduction

Lung cancer one of 3 most common cancers

Lacks effective screening program (unlike cacervix and ca breast)

Abnormal nodule in chest radiograph

Worked up by bronchoscopy and imagingguidance for cytologic material and by

biopsy


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Bronchoscopy: history

Killian (1885): translaryngeal approach for removalof foreign body

Jackson (1917): use of light at an end; peroral route;use for diagnosis and therapeutic purposes

Until 1960s: rigid bronchoscopes; limited access todistal airways

Machida (1968): first flexible/fibreopticbronchoscope (FOB)

Newer applications: Video bronchoscopy,bronchoscopic USG, fluorescence bronchoscopy,virtual bronchoscopy


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Pathologic specimens in

diagnosis of lung diseases Cytologic specimens (exfoliative, FNA):

Sputum (pre- and post-FOB)

BW

BAL

BB

FNA: TBNA, EBUS FNA, TTNA Biopsy specimens:

Forceps biopsy ((endobronchial, transbronchial)

Added techniques: imprint smears, rinse fluid


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Cytologic features: Sputum

Direct smears; stained with H&E and/or Pap

Mucus

Pulmonary alveolar macrophages

Pigmented macrophages

Bronchial epithelial cells

Upper respiratory tract squames Candida hyphae, spores

Charcot-Leyden crystals


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Cytologic features: BB

BB obtained by gently rolling over on the slidehaving 95% alcohol

BB better if taken before other procedures (BW,BAL, Bx)

Bronchial epithelial cells as sheets and plenty ofseparated cells

Goblet cell metaplasia may be seen

Upper respiratory squames seen

Metaplastic sq cells present

Pulmonary alveolar macrophages+ but < BAL, BW


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Cytologic features: BW

Direct smears at FOB (except in LBC)

Similar to sputum specimens except thatepithelial cells are more numerous


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Cytologic features: BAL

Thinner, less mucoid

Cytocentrifugation Pulmonary macrophages comprise 80% of

cells; others are inflammatory cells (PMNs,

L) and bronchial epithelial cells


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Needle aspiration

FOB: TBNA

Under imaging guidance

EUS-FNA

Direct smears; air-dried for MGG and Diff-Quik, alcohol fixed for Pap and H&E

Needle washings in formalin as cell block forICC


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Bronchial Bx

Paraffin-embedding technique

Gold standard versus longer TAT Additional uses: imprint, rinse fluid

Lower sensitivity, higher diagnostic yield

Cytologic-negative and histologic-positivecases


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Imprint (Touch) smears

Biopsied tissue imprinted on slides

Cell distribution and tissue architecture better Quality determining factors: fixation, speed

of imprinting, thickness of smears, bloody

smears, inflammatory cells, necrosis


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Rinse fluid

As exfoliative cytology: suspended in BSS

Described in many organs as biopsy-cytologytechnique

Advantages in pulmonary cytology:

distinctive cellular features in isolated cells,ICC


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Applications of cytohistologic

specimens in lung lesions

Neoplastic: Sq cell ca, adenoca, small cell ca,

large cell ca, carcinoid, metastasis

Nonneoplastic infectious: Abscess, TB,

fungi, aspergillosis, candida, mucor, hydatid

Nonneoplastic noninfectious: ILDs,Wegeners granulomatosis


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Combining cytohistologic techniques in

lung tumours: our experience

Increased diagnostic yield

Specificity=100%

Methods Sensitivity

BAL+BB = 72.9%

BB+FBx = 84.5%

BB+FBx+TBNA = 87.5% TTNA = 77.8%

Alone: sputum=27.6%; BAL=37.5%; BB=70%;TBNA=83.3%

Garg et al.Diagn. Cytopathol. 2007;35:26-31


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Combining cytohistologic techniques in TBlung: our experience

Specimen Sensitivity

BAL 80%

BB 60%

Post-FOB 45%

Bx 87%

Specificity =100% in all

Garg et al.Diagn. Cytopathol. 2007;35:26-31


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Statistical analysis of rinse fluid and imprintsmear examination: our experience

Sensiti-

vity %

Specifi

-city %

PPV

%

NPV % Diagn

acc %

K test

Rinse fluid 75 100 100 61.1 78.84 0.454

Imprintsmears

97.8 100 100 87.5 98.08 0.922

Goyal et al.Diagn. Cytopathol. 2012; 3:165-7


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What is new in pathology of

lung tumours ? Terms BAC and mixed type not used

NSCC categories: adenoca, sq cell ca, large cell ca.

SCC categories: pure, combined

Adenoca in situ: with lepidic growth pattern insmall solitary ca (


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Newer categories ofadenoca. classification

(formerly BAC)1. Adenoca in situ, non-mucinous and rarely

mucinous

2. Minimally invasive adenocarcinoma, non-mucinous and rarely mucinous

3. Lepidic predominant adenocarcinoma, non-mucinous

4. Adenocarcinoma, predominantly invasive withsome non-mucinous lepidic component(formerly mixed subtype and non-mucinousBAC)

5. Invasive mucinous adenocarcinoma (formerly


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Newer categories of

other NSCC lung Sq cell ca: subtypes

Papillary

Clear cell Small cell

Basaloid

Large cell ca: subtypes

Large cell NE ca

Large cell ca with NE morphology

Others:

Adenosquamous ca

Sarcomatoid


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New in small cell ca lung

Older classification:

Oat cell

Intermediate

Combined

Current:

Pure

Combined (containing any other NSCC component)


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A quick round of morphology

Neoplasms


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Bronchial carcinoid

Typical and atypical carcinoids low grade NEtumour (low mitotic and proliferation rates, less and

focal necrosis) Organoid pattern, uniform tumour cells; other

patterns: spindle cells, trabecular, palisading,rosette-like, papillary, follicular

Finely granular nuclear chromatin, moderatecytoplasm

IHC: Ki-67, NE markers (chromogranin,synaptophysin,CD56)


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Bronchial carcinoid:

cytologic features Cells smaller, round to oval

Nucleus: granular chromatin, 1-2 nucleoli;little evidence of moulding, pleomorphism or

necrosis

Cytoplasm: scanty, delicate, red granular


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Small cell ca lung

Patterns: diffuse sheets; others rosettes,palisading, organoid, streams, ribbons

Nuclear moulding, crushing artifacts

Small cells, round to fusiform nucleus,inconspicuous or absent nucleoli

Necrosis frequent and extensive

Cytology versusbiopsy


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Small cell ca: cytologic features

Isolated and small groups of cells, small and

intermediate in size

Cellular features: Scanty cytoplasm, nuclear

crushing artefacts, salt and pepper chromatin,

nuclear moulding, inconspicuous or absent nucleoli,

high mitoses Fragmented cells and necrosis in background

Paranuclear blue (inclusion) bodies


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Adenocarcinoma

Currently most common lung cancer

Adenoca in situ, minimally invasive,invasive

Mucinous, non-mucinous

Primary, metastatic Patterns of adenoca.


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Adenocarcinoma:

cytologic features Cohesive groups of cells

Patterns: acinar, papillary, micropapillary

Cytoplasmic vacuoles in some cells

Occasionally mucinous background

Subclassification based on above features


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Adenoca with

lepidic growth pattern Formerly bronchioloalveolar ca.

Monotonous population of atypical bronchiolo-

alveolar cells in monolayered sheets and papillae

Nuclear features: bland nuclei, nuclear clearing,

chromatin margination, intranuclear cytoplasmic

pseudoinclusions, nuclear grooves Psammoma bodies sometimes


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Sq cell ca lung

May be a classic NSCC: keratinising, non-

keratinising; varying grades of differentiation

May require distinction from small cell ca

and basaloid variant of large cell ca


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Sq cell ca: cytologic features

Cohesive groups and isolated pleomorphic

cells

Cellular features: hyperchromatic nuclei,

uniformly dense and focally eosinophilic

cytoplasm

Necrotic debris in background common


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Large cell ca: cytologic features

Poorly-differentiated non-small cell unclassifiable ca

Absence of squamous/glandular differentiation

Isolated cells and small cell clusters

Cellular features: large, pleomorphic nuclei,

parachrmatin clearing, presence of macronucleoli,

binucleation/ multinucleation common, N:C ratiolow


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IHC in various types of ca lung

Cancer type CK7 HMW-

CK5/6

TTF-1 p63

Adeno ca. + _ + _

Sq cell ca. _ + _ +

Small cell ca.* + _ + _

*NE markers + (chromogranin, NSE, synaptophysin)


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A quick round of morphology

Non-neoplastic lesions:infectious and noninfectious


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Tuberculosis: cytologic features

Epithelioid cell granulomas

Mixed inflammation; sometimes pus

Langhans giant cells

Caseation necrosis

AFB in ZN stain


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Others

Fungal infections: aspergillosis, mucor

Hydatid cyst

Wegeners granulomatosis

ILDs


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Diagnostic pitfalls in

pulmonary cytology Problems of false positive more serious than

false negative

Mimics mistaken for bronchogenic ca:

Reactive atypia secondary to inflammation

Reactive type II pneumocytes

Basal cell hyperplasia

Reactive squamous metaplasia


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Molecular diagnostics in

respiratory pathologyNeed to categorise lung cancer into not only

small cell and non-small cell type but also

further subtypes of the latter.

For targeted therapy and predicting

prognosis: molecular testing forEGFR and

KRASmutation,ALKrearrangement.


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04 diagnostic value of cytohistopathologic specimens obtaine

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